Cross protection among the togaviruses in each major group occurs in the absence of cross neutralizing antibody. We have reported that cell mediated immunity may play an important role in cross protection among alphaviruses since such immunity could be passed to recipients by adoptive transfer of T-lymphocyte-enriched spleen cell populations. It is our primary goal to confirm and extend these observations in vivo and in vitro and to elucidate the mechanisms, and possibly elaborate on the antigen(s) involved. We have also reported that antibody-dependent, complement-mediated cross cytolysis can be demonstrated to infected cell cultures but we do not believe that this mechanism plays an important role in vivo. Nevertheless, we will study the cross ADCMC for its own sake and in preparation for comparing it to the cross reacting antigen(s) involved in cell mediated immunity and cross protection. Our main approach in studying CMI in vivo will emphasize the recipient which permits us to focus on CMI in the absence of antibody. We will also use a nude-littermate mouse model to gain independent evidence for the role of CMI in cross protection that may be antibody independent and/or antibody dependent by ADCC. In our tests for correlates of CMI in vitro, we will use temperature sensitive (ts) RNA plus mutants, not only to enhance our ability to demonstrate cross cytolysis of infected cells, but also as an approach towards identifying the plasma membrane virus-induced antigen(s) involved. We also expect to make use of certain restrictions imposed by the H-2 complex in the mouse response to infections in vivo, in demonstrating correlates of CMI in vitro, and in elucidating an allogeneic effect we have found. Our long range goal is to apply the knowledge of all the mechanisms of cross protection among togaviruses to develop a broad spectrum vaccine using a minimum number of avirulent viruses or viral specific-antigens.